Efficacy of a yeast postbiotic on cold/flu symptoms in healthy children: A randomized-controlled trial.

BACKGROUND: Children attending school/daycare are at high risk of acute respiratory tract infections. EpiCorTM postbiotic, derived from yeast fermentate, has been demonstrated to improve immune function in adults, reducing the incidence of cold/flu-like or allergy symptoms. As such, studies are warranted in children as available pharmaceutical options have unwanted side effects. METHODS: Two-hundred and fifty-six children aged 4-12 years attending school/daycare were randomized to either EpiCor or Placebo for 84 days during the 2022-2023 flu season in Ontario, Canada. The Canadian Acute Respiratory Illness and Flu Scale (CARIFS) and study diary assessed the incidence and severity of cold/flu symptoms and the use of cold/flu medications. Adverse events were recorded. RESULTS: Total CARIFS severity scores, 'sore throat' and 'muscle aches or pains' symptom scores in the EpiCor group were significantly lower compared to Placebo during incidences of cold/flu (P ≤ 0.05). Participants taking Placebo were 1.73 times more likely to use cold/flu medication compared to those receiving EpiCor (P = 0.04). The incidence of cold/flu symptoms was not significantly different between groups. EpiCor was found to be safe and well-tolerated. CONCLUSIONS: EpiCor supplementation resulted in significantly lower cold/flu symptom severity and less cold/flu medication usage than Placebo demonstrating a beneficial effect on immune function in children. IMPACT: Children are at high risk of acquiring cold/flu infections and safe and efficacious mitigating regimens are lacking. Children supplemented daily with 500 mg EpiCorTM postbiotic derived from yeast fermentate had significantly lower overall cold/flu symptom severity, and severity of sore throat and muscle aches or pains over the 84-day supplementation period. EpiCor supplementation resulted in decreased use of traditional cold/flu medication. Daily supplementation with 500 mg of EpiCor for 84 days was safe and well tolerated by healthy children aged 4-12 years attending school or daycare.

Consuming a Protein and Fiber-Based Supplement Preload Promotes Weight Loss and Alters Metabolic Markers in Overweight Adults in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Higher protein and fiber diets promote weight management and metabolic health. OBJECTIVES: This study aimed to determine if greater weight loss and positive changes in metabolic outcomes could be achieved with twice-daily consumption of a high-protein and fiber-based multi-ingredient nutritional shake (HPF) compared with an isocaloric low-protein, lower fiber-based placebo (LPF). METHODS: Study procedures were conducted by an independent research organization under clinicaltrials.gov registration NCT03057873. Healthy overweight and obese adults [n = 206; BMI (kg/m2): 27-35; 70% female] were randomly assigned to HPF or LPF. All participants were prescribed an energy-restricted diet (500 kcal/d less than energy needs) and consumed a HPF (17 g protein, 6 g fiber) or LPF (1 g protein, 3 g fiber) shake 30 min before breakfast and lunch for 12 wk. Primary outcomes included body weight and total body fat percentage. Blood samples were collected at days (D) 0, 28, 56, and 84 for secondary analyses related to metabolic markers of health. RESULTS: Although weight loss occurred in both groups, HPF had greater weight loss at D84 compared with LPF (-3.3 kg vs. -1.8 kg, P < 0.05). Percentage body fat decreased in both groups (HPF: -1.33%, LPF: -1.09%; P < 0.001) with no differences between groups. Serum total cholesterol, LDL cholesterol, and oxidized LDL decreased between -5.1% to -8.3%, whereas adiponectin increased over time in both groups; these changes occurred to a greater extent in HPF compared with LPF (all P < 0.05). CONCLUSIONS: A multi-ingredient HPF nutritional supplement shake consumed as a preload before breakfast and lunch positively influenced weight management and metabolic outcomes in overweight adults compared with an LPF placebo. These findings suggest that specific nutrient factors (i.e., potentially including protein, fiber, and bioactive content) other than calorie reduction alone influence the success of a weight-loss regimen. This trial was registered at www.clinicaltrials.gov as NCT03057873.

A Randomized, Double-blind, Placebo-controlled, Parallel Study Evaluating the Efficacy of Bacillus subtilis MB40 to Reduce Abdominal Discomfort, Gas, and Bloating.

INTRODUCTION: Bloating is a common yet poorly managed complaint among healthy people, with a complex etiology that impacts health and general well-being. The study intended to evaluate the efficacy and safety of supplementation with a probiotic, Bacillus subtilis MB40 (MB40), on bloating, abdominal discomfort, and gas in healthy participants. METHODS: In this multi-center, double-blind, placebo-controlled, parallel trial, 100 participants were randomized to receive either MB40 at 5 × 109 colony forming units (CFU; n = 50) or a placebo (n = 50) once daily for 4-weeks. Participants completed 3 questionnaires daily: a modified Abdominal Discomfort, Gas, and Bloating (mADGB) questionnaire, a modified Gastrointestinal Symptoms Rating Scale (mGSRS), and a Bowel Habits Diary (BHD). Participants' responses to each question were combined into weekly averages. RESULTS: At the end of 4-weeks, there were no significant differences in average weekly change in daily bloating intensity, number of days with and duration of bloating, abdominal discomfort and gas between MB40 and placebo groups. However, the male sub-group on MB40 achieved clinical thresholds with a greater decrease over placebo in the intensity of (1.38) and number of days with (1.32) bloating, the number of days (1.06) and duration (86-minutes) of gas, the number of days with abdominal discomfort (1.32) and diarrhea symptom score (1.02). Role limitation (physical; P = .026), vitality (P = .034) and social functioning (P = .037) were significantly improved from baseline to week 4 in the MB40 group. At 2-weeks, physical functioning (P = .017) significantly improved in the MB40 group versus placebo. CONCLUSIONS: Although MB40 supplementation did not significantly improve bloating across all populations, the male sub-group demonstrated clinically significant reductions in bloating intensity, number of days with abdominal discomfort, gas, bloating, and duration of gas, compared to placebo. Additionally, the male sub-group receiving MB40 had a 10% improvement in general health score. MB40 supplementation at a dose of 5 × 109 CFU daily for 4-weeks was also safe and well-tolerated as all biometric, vital, and hematological measures remained within normal laboratory ranges (Clinical Trials NCT02950012).

Vitamin C Bioequivalence from Gummy and Caplet Sources in Healthy Adults: A Randomized-Controlled Trial.

Background: The efficacy of Vitamin C (L-ascorbic acid) supplementation can be assessed by uptake into the blood and retention in leukocytes. Vitafusion® Power C gummy is an alternative vitamin C source which may exhibit similar bioavailability to comparator caplets.Objective: The objective of this study was to evaluate the bioequivalence of vitamin C from a vitafusion® Power C gummy formulation and a comparator caplet in healthy adults.Methods: Thirty healthy men and women, 34.0 ± 11.4 years of age and Body Mass Index (BMI) 24.5 ± 3.6 kg/m2 completed the randomized examiner-blind, comparator controlled, cross-over trial with two sequences: gummy (1000 mg) to caplet (1000 mg) or caplet to gummy. Intake of foods fortified with Vitamin C was restricted 7 days prior to each dosing. Blood samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 h post-dose for plasma and leukocytes; and urine was collected pre-dose and between 0-2, 2-4, 4-8, 8-12 and 12-24 h post-dose for L-ascorbic acid analysis.Results: Vitafusion® Power C gummy and comparator caplet demonstrated similar plasma absorption profiles as there were no significant differences in plasma L-ascorbic acid total Area Under the Curve (AUC)0-24h, and Tmax between gummy and caplet. The caplet did elicit a significantly higher Cmax than the gummy (p < 0.05), however, the difference was numerically small. Leukocyte L-ascorbic acid total AUC0-24h and Cmax were not significantly different between gummy and caplet, however Tmax of the gummy group was significantly longer (p = 0.012). Urinary L-ascorbic acid levels were also not significantly different between gummy and caplet. There were no serious adverse events and safety parameters remained within normal clinical range for both products.Conclusion: Vitafusion® Power C gummy exhibited similar Vitamin C absorption and bioavailability to a comparator caplet in healthy adults and were considered bioequivalent.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

OBJECTIVE: The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. RESULTS: Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. CONCLUSION: These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

An open label pilot study to evaluate the efficacy of Spanish black radish on the induction of phase I and phase II enzymes in healthy male subjects.

BACKGROUND: Humans are exposed to toxins which accumulate in the body, and are detoxified primarily in the liver. Studies have shown that cruciferous vegetables (such as radishes) may be beneficial to health by aiding detoxification of toxins in the liver. METHODS: This single-centre, open-label, pilot study investigated the effect of a dietary supplement containing Spanish Black Radish on hepatic function in healthy males by monitoring the profiles of plasma and urine acetaminophen metabolites and serum hormone concentrations at baseline and after 4 weeks of supplementation. A paired t-test was used to compare pre- and post-treatment of plasma and urine acetaminophen metabolite profiles, serum hormone concentrations and safety end points. RESULTS: Area under the curve (AUC) from 0 to 8 hours for the acetaminophen glucuronide metabolite and unchanged acetaminophen in plasma decreased from baseline to week 4 by 9% (P = 0.004) and 40% (P = 0.010), respectively. The AUC from 0 to 8 hours for acetaminophen sulfate and mercapturate metabolites in the urine increased by 11% (P = 0.010) and 37% (P = 0.024), respectively, from baseline to week 4. The AUC from 0 to 8 hours of serum estradiol-17ß decreased by 10% from baseline to week 4 (P = 0.005). All measures of clinical safety remained within acceptable laboratory ranges, however a significant reduction in plasma γ-glutamyl transferase levels was noted after 4 weeks of Spanish Black Radish treatment (P = 0.002). CONCLUSIONS: These changes in metabolite and hormone levels indicate that Spanish Black Radish supplements have a positive influence on the detoxification of acetaminophen suggesting up-regulation of phase I and phase II liver enzymes. This study was sponsored by Standard Process Inc. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02137590 (Date of registration: May 12, 2014).

Efficacy of Pea Protein Supplementation in Combination with a Resistance Training Program on Muscle Performance in a Sedentary Adult Population: A Randomized, Comparator-Controlled, Parallel Clinical Trial.

Animal-sourced whey protein (WPr) is the most popular protein supplement among consumers and has been shown to improve muscle mass and strength. However, due to allergies, dietary restrictions/personal choices, and growing demand, alternative protein sources are warranted. Sedentary adults were randomized to pea protein (PPr) or WPr in combination with a weekly resistance training program for 84 days. Changes in whole-body muscle strength (WBMS) including handgrip, lower body, and upper body strength, body composition, and product perception were assessed. The safety outcomes included adverse events, vital signs, clinical chemistry, and hematology. There were no significant differences in the change in WBMS, muscle mass, or product perception and likability scores between the PPr and WPr groups. The participants supplemented with PPr had a 16.1% improvement in WBMS following 84 days of supplementation (p = 0.01), while those taking WPr had an improvement of 11.1% (p = 0.06). Both study products were safe and well-tolerated in the enrolled population. Eighty-four days of PPr supplementation resulted in improvements in strength and muscle mass comparable to WPr when combined with a resistance training program in a population of healthy sedentary adults. PPr may be considered as a viable alternative to animal-sourced WPr without sacrificing muscular gains and product enjoyment.

Revisiting the Definition of 'Healthy' Participants in Substantiation of Structure/Function Claims for Dietary Supplements.

Concepts and definitions of 'healthy' have been evolving within clinical treatment algorithms as well as reference standards such as Body Mass Index and Dietary Reference Intakes. Consumers' perception of the word 'healthy' is also changing to reflect longer life span, need to stay active and in a good state of mental well-being while managing multiple diseases. Guidelines from the US Food and Drug Administration indicate that substantiating evidence for support of Structure/Function (S/F) claims for dietary supplements is best derived from clinical research conducted in a 'healthy' population. S/F claims cannot be represented to diagnose, treat, cure or prevent any disease. However, in this context, the term 'healthy' is non-descriptive and largely interpreted as an absence of disease. Guidelines for treatment of disease have been broadened to include biomarkers of disease risk such that the pool of 'healthy' volunteers eligible to be enrolled in clinical trials for S/F claim substantiation is greatly diminished. This perspective presents the challenges faced by the food and dietary supplement industry and by researcher efforts designed to substantiate S/F claims and suggest the phrase 'physiologically stable' or 'apparently healthy' as descriptions better suited to replace the term 'healthy.'

Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

PURPOSE: Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. METHODS: Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. RESULTS: The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. CONCLUSION: These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

Role of Acacia catechu and Scutellaria baicalensis in Enhancing Immune Function Following Influenza Vaccination of Healthy Adults: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: The study aimed to examine the role of an Acacia catechu and Scutellaria baicalensis formulation, UP446, on supporting immune function in response to influenza vaccination. METHODS: A randomized, triple-blind, placebo-controlled, parallel study consisted of a 56-day intervention period with a 28-day pre-vaccination period, an influenza vaccination on Day 28 and 28-day post-vaccination period. Fifty healthy adults 40-80 years of age who had not received their flu vaccine were randomized to either UP446 or Placebo. At baseline, Days 28 and 56, immune and oxidative stress markers were measured in blood and a quality of life questionnaire was administered. Participants completed the Wisconsin Upper Respiratory Symptom Survey (WURSS)-24 daily. RESULTS: In the post-vaccination period, total IgA and IgG levels increased in participants supplemented with UP446 vs. those on Placebo (p ≤ 0.026). As well, influenza B-specific IgG increased 19.4% from Day 28 to 56 and 11.6% from baseline at Day 56 (p ≤ 0.0075). Serum glutathione peroxidase (GSH-Px) was increased in the pre-vaccination period and from baseline at Day 56 with UP446 supplementation (p ≤ 0.0270). CONCLUSION: These results suggest a 56-day supplementation with UP446 was beneficial in mounting a robust humoral response following vaccination. Increasing GSH-Px in the pre-vaccination period may help improve antioxidant functions and potentially mitigate the oxidative stress induced following vaccination.

Healthy adults supplemented with a nutraceutical formulation containing Aloe vera gel, rosemary and Poria cocos enhances the effect of influenza vaccination in a randomized, triple-blind, placebo-controlled trial.

The study objective was to examine the role of a formulation, UP360, containing rosemary and Poria cocos extracts and Aloe vera gel powder, in healthy adults on supporting immune function with influenza vaccination. A 56-day randomized, triple-blind, placebo-controlled, parallel study consisted of a 28-day pre-vaccination period, an influenza vaccination on Day 28 and a 28-day post-vaccination period. Men and women ages 40-80 who had not yet been vaccinated for the flu were randomized to UP360 or Placebo (n = 25/group). At baseline, Days 28 and 56, blood lymphocyte populations, immunoglobulins (Ig), and cytokines were measured, and quality of life (QoL) questionnaires administered. The Wisconsin Upper Respiratory Symptom Survey (WURSS)-24 was completed daily by participants to measure incidence of upper respiratory tract infection (URTIs). In the post-vaccination period, TCR gamma-delta (γδ+) cells, known as γδ T cells, increased with UP360 supplementation compared to Placebo (p < 0.001). The UP360 group had a 15.6% increase in influenza B-specific IgG levels in the post-vaccination period (p = 0.0006). UP360 significantly increased the amount of circulating glutathione peroxidase (GSH-Px) from baseline at Day 28 (p = 0.0214), an enzyme that is important for neutralizing free radicals. While UP360 supplementation initially decreased levels of anti-inflammatory cytokine IL-1RA in the pre-vaccination period, IL-1RA levels were increased in the post-vaccination period (p ≤ 0.0482). Levels of IL-7 increased from baseline at Day 56 with UP360 supplementation (p = 0.0458). Despite these changes in immune markers, there were no differences in URTI symptoms or QoL between UP360 and Placebo. These results suggest UP360 supplementation was beneficial in eliciting a healthy, robust immune response in the context of vaccination. No changes in subjective measures of URTI illness or QoL demonstrated that participants' QoL was not negatively impacted by UP360 supplementation. There were no differences in clinical chemistry, vitals or adverse events confirming the good safety profile of UP360. The trial was registered on the International Clinical Trials Registry Platform (ISRCTN15838713).

A randomized, double-blind, placebo-controlled, cross-over pilot study to investigate the efficacy of Rest-ZZZ formula in healthy participants with occasional sleeplessness.

The purpose of this study was to investigate the safety and efficacy of Rest-ZZZ, a natural sleep supplement, in healthy adults without a diagnosed sleep disorder. This randomized, double-blind, placebo-controlled, cross-over study consisted of three 7-day supplementation periods with either Rest-ZZZ, Diphenhydramine (DPH), or Placebo, with a 7-day washout. Twenty-seven participants were randomized to one of three intervention sequences and the Healthy People Sleep Quality Index (HPSQI), Quality of Life (QoL), and Profile of Mood States (POMS) questionnaires were assessed at the beginning and end of each supplementation period. Rest-ZZZ and Placebo showed improvements in sleep-related QoL (p ≤ 0.044) and total mood disturbance (TMD) (p = ≤ 0.028). Fatigue-Inertia was reduced by all study products (p ≤ 0.031). DPH did not result in any significant improvements on sleep quality parameters. A subgroup analysis of participants ≤ 45 years found enhanced efficacy of Rest-ZZZ and improvement in sleep-related QoL vs. Placebo (p = 0.007), as well as improvements in sleep duration (p = 0.007), sleep debt (p = 0.011), and sleep-related QoL (p = 0.033). DPH supplementation resulted in significant improvement in only sleep debt (p = 0.038). Rest-ZZZ had a safe hematology and chemistry profile. Rest-ZZZ resulted in restful sleep that generated corresponding improvements in sleep-related QoL and overall mood. Rest-ZZZ is an efficacious sleep supplement with a favorable safety profile, particularly in those aged 25-45 years.

Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study.

INTRODUCTION: Transdermal cannabinoids may provide better safety and bioavailability profiles compared with other routes of administration. This single-arm, open-label study investigated a novel topical transdermal delivery system on the pharmacokinetics of cannabidiol (CBD) and tetrahydrocannabinol (THC). METHODS: Participants were 39.5 ± 7.37 years old and healthy, based on a review by the Medical Director. Blood was collected pre-dose and 10, 20, 30, and 45 min, and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h after topical application of 100 mg CBD:100 mg THC. Psychoactive effects were assessed prior to each timepoint. Area-under-the-curve (AUC0-12 h), maximum concentration (Cmax), time to maximum concentration (Tmax), area-under-the-curve to infinity (AUCI), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (ka) were measured individually for CBD and THC. Safety was assessed by clinical chemistry, hematology, and adverse events. RESULTS: AUC0-12 h for CBD and THC was 3329.8 ± 3252.1 and 2093.4 ± 2090.6 pg/mL/h, with Cmax of 576.52 ± 1016.18 and 346.57 ± 776.85 pg/mL, respectively. Tmax for CBD and THC was 8 h, ranging from 2.5 h to 12 h and 10 min to 12 h, respectively. AUCI for CBD and THC was 6609.2 ± 7056.4 and 3721.0 ± 3251.7 pg/mL/h, with t1/2 of 5.68 ± 1.5 and 5.38 ± 1.25 h, respectively. CBD was absorbed at a faster rate compared with THC (123.36 ± 530.97 versus 71.5 ± 1142.19 h-1) but with similar λ (0.12 ± 0.029 versus 0.13 ± 0.03 h-1). No psychoactive effects were reported. Transdermal cannabinoid delivery was safe and well tolerated in the population studied. CONCLUSION: To our knowledge, this is the first pharmacokinetic study in humans that demonstrated CBD and THC entering systemic circulation via transdermal administration . This study represents an important contribution to understanding the pharmacokinetics of transdermal cannabinoids. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier-NCT05121506 (November 16, 2021).

A Randomized, Double-Blind, Placebo-Controlled, Parallel Study Investigating the Efficacy of a Whole Coffee Cherry Extract and Phosphatidylserine Formulation on Cognitive Performance of Healthy Adults with Self-Perceived Memory Problems.

INTRODUCTION: Cognition refers to brain functions including memory, learning, and thought processing and is increasingly important to individuals. However, impairment of cognitive function is a concern among North American adults. Therefore, effective and reliable treatments are needed. METHODS: This randomized, double-blind, placebo-controlled study examined the effects of 42 days of Neuriva® supplementation, a whole coffee cherry extract and phosphatidylserine supplement, on memory, accuracy, focus and concentration and learning among 138 healthy adults (40-65 years) with self-reported memory problems. Plasma brain-derived neurotrophic factor (BDNF) levels, Computerized Mental Performance Assessment System (COMPASS) tasks, the Everyday Memory Questionnaire (EMQ), and Go/No-Go tests were assessed at baseline and day 42. RESULTS: As compared to placebo, Neuriva® supplementation elicited greater improvements at day 42 in numeric working memory COMPASS task accuracy outcomes (p ≤ 0.024) which assessed memory, accuracy, and focus and concentration, and reaction time outcomes (p ≤ 0.031) which assessed memory as well as focus and concentration. Neuriva® supplementation improved overall accuracy (p = 0.035) in the picture recognition task that assessed memory, accuracy, and learning compared to placebo. No significant differences between groups were observed for BDNF, the EMQ, or Go/No-Go tests. CONCLUSION: Results suggest 42 days of Neuriva® supplementation was safe, well tolerated, and beneficial in improving memory, accuracy, focus and concentration, and learning in a healthy adult population with self-reported memory problems.

Bioavailability of calcium in an enriched postbiotic system compared to calcium citrate in healthy postmenopausal females; A randomized, double-blind, comparator-controlled, crossover study.

Introduction: Bioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women. Methods: A total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively. Results: Ca-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study. Discussion: These findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.

A dried yeast fermentate prevents and reduces inflammation in two separate experimental immune models.

Diverse and significant benefits against cold/flu symptoms and seasonal allergies have been observed with a dried fermentate (DF) derived from Saccharomyces cerevisiae (EpiCor) in multiple published randomized trials. To determine if DF may influence other immune conditions, two separate animal studies were conducted. Study 1 examined the ability of DF to prevent or reduce inflammation when given orally for 14 days to rats prior to receiving 1% carrageenan (localized inflammation model). DF significantly (P < 0.05) reduced swelling at all time points (1, 2, 3, 6, 12, and 24 hours) versus the control. Edema severity and PGE2 levels were reduced by approximately 50% and 25% (P < 0.05), respectively. Study 2 examined the ability of DF to treat established inflammation induced by type-2 collagen in mice over 4 weeks (autoimmune arthritis model). Significantly reduced arthritis scores, antibody response to type-2 collagen, and interferon-gamma levels were observed compared to controls (all parameters P < 0.05). DF favorably impacts multiple acute and potentially chronic immunologic inflammatory control mechanisms and should be further tested in clinical trials.

A Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History.

Background: An oral route of administration for tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) eliminates the harmful effects of smoking and has potential for efficacious cannabis delivery for therapeutic and recreational applications. We investigated the pharmacokinetics of CBD, Δ9-THC, 11-OH-THC, and 11-nor-9-carboxy-Δ9-THC (THC-COOH) in a novel oral delivery system, Solutech™, compared to medium-chain triglyceride-diluted cannabis oil (MCT-oil) in a healthy population. Materials and Methods: Thirty-two participants were randomized and divided into two study arms employing a comparator-controlled, parallel-study design. To evaluate the pharmacokinetics of Δ9-THC, CBD, 11-OH-THC, and THC-COOH, blood was collected at pre-dose (t=0) and 10, 20, 30, and 45, min and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, and 48 h post-dose after a single dose of Solutech (10.0 mg Δ9-THC, 9.76 mg CBD) or MCT (10.0 mg Δ9-THC, 9.92 mg CBD). Heart rate and blood pressure were measured at 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h. Relationships between cannabis use history, body mass index, sex, and pharmacokinetic parameters were investigated. Safety was assessed before and at 48 h post-acute dose. Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001). In addition, cannabis use history had a significant influence on the pharmacokinetic parameters of CBD, Δ9-THC, 11-OH-THC, and THC-COOH. On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032). Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048). Conclusion: This study demonstrated that consumption of Solutech enhanced most pharmacokinetics parameters measured compared to MCT-oil. Participant's cannabis use history, including their age of first use and number of years using cannabis significantly impacted pharmacokinetic parameters investigated. Acute consumption of both products was found to be safe and well tolerated. The results suggest that Solutech may optimize bioavailability from cannabis formulations.

Breaking new frontiers: Assessment and re-evaluation of clinical trial design for nutraceuticals.

Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals.

Examining the Efficacy of a Very-Low-Carbohydrate Ketogenic Diet on Cardiovascular Health in Adults with Mildly Elevated Low-Density Lipoprotein Cholesterol in an Open-Label Pilot Study.

Background: The objective of this open-label pilot study was to investigate the efficacy of a very-low-carbohydrate ketogenic diet (VLCKD), known as Nic's Ketogenic Diet, for 140 days on cardiometabolic markers in healthy adults with mildly elevated low-density lipoprotein cholesterol (LDL-C). Methods: Study assessments were conducted at Day 0, 28, 56, 70, 84, 112, and 140, and weight and blood pressure (BP) were measured and fasting blood was collected for analysis of plasma lipids. A DEXA scan was performed and body mass index recorded on Day 0, 70, and 140. Blood glucose, inflammatory, and thyroid markers were measured on Day 0 and 140. Compliance was assessed using weekly 3-day food records and daily blood glucose and ketone monitoring. Results: The results showed that body fat percentage decreased by 2.25% and 4.41% at Day 70 and 140, respectively (P ≤ 0.012). Significant reductions in android, gynoid, and android/gynoid fat ratio and increases in muscle mass occurred by Day 70 and 140. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol were increased and systolic BP and glycated hemoglobin (HbA1c) were decreased at Day 140 (P < 0.05). Following this VLCKD for 140 days was found to be safe and was well tolerated. Conclusion: The VLCKD showed beneficial changes in body composition and cardiometabolic markers in eutrophic and overweight participants in a 140-day study suggesting a future role for this diet in populations at cardiovascular disease risk. Future research with larger sample size in a randomized double blind clinical trial is warranted to confirm these results. Clinical Trial Registration number: NCT04195594.